Autosomal-recessive charcot-marie-tooth diseases

• Published in: Journal of neuropathology and experimental neurology Vol. 64; no. 5; pp. 363 - 370
• Main Authors: VALLAT, Jean-Michel, TAZIR, Meriem, MAGDELAINE, Corinne, STURTZ, Franck, GRID, Djamel
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-05-2005; Oxford University Press
• Subjects: Biological and medical sciences; Charcot-Marie-Tooth Disease - classification; Charcot-Marie-Tooth Disease - epidemiology; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Demyelinating Diseases - epidemiology; Demyelinating Diseases - genetics; Demyelinating Diseases - pathology; Disorders of higher nervous function. Focal brain diseases. Central vestibular syndrome and deafness. Brain stem syndromes; Genes, Recessive; Humans; Medical sciences; Mutation; Myelin Sheath - pathology; Myelin Sheath - ultrastructure; Nervous system (semeiology, syndromes); Neurology; Hereditary sensory-motor neuropathy; Neuromuscular diseases; Nervous system diseases; Charcot-Marie-Tooth; Neuropathy; Nerve biopsy; Recessive neurological diseases; Genetic disease; Charcot Marie Tooth disease; Biopsy; Central nervous system disease; Genetic analysis; Genetics; Degenerative disease; Spinal cord disease
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/64.5.363

In certain countries around the Mediterranean basin such as Algeria, which have a high prevalence of consanguineous marriages, autosomal-recessive (AR) inheritance may account for more than 50% of all forms of Charcot-Marie-Tooth (CMT) disease. Like with the dominant forms, it is usual to differentiate the demyelinating forms (CMT 4 corresponding to autosomal-recessive CMT 1 [AR-CMT 1] from the axonal forms [AR-CMT 2]). Genetic analysis of large families with recessive transmission has uncovered novel CMT genotypes (genes: GDAP 1, MTMR 2, MTMR 13, KIAA1985, NDGR1, periaxi, lamin). The clinical and especially the histologic phenotypes often indicate that a specific gene is implicated. We present and discuss microscopic lesions seen on nerve biopsies from patients in a number of consanguineous Algerian families, and we outline the characteristic lesions that would prompt a search for mutations in genes such as MTMR 2, MTMR 13, KIAA1985, periaxin for CMT 4, and lamin for AR-CMT 2. Like with the dominant forms, there are undoubtedly many more mutations of other genes to be discovered.